Abstract
Micelleplexes are constructed from multiarmed amphiphilic copolymers with conjugation of captothecin (CPT) and condensation of tumor necrosis factor-α (TNF) plasmid. The pH/redox stimuli realize co-delivery of CPT and pDNA in a sequential manner of folate-mediated endocytosis, endosomal escape induced by PEG cleavage, reduction-sensitive release of CPT in cytosol, and pDNA release from disintegrated polyplexes after CPT release. Compared with CPT or TNF treatment alone, the micelleplexes achieve 2.5 and 8 folds higher cytotoxicities to tumor cells, and suppress the tumor growth with 2.3 and 3 folds lower in volume, respectively. It demonstrates a feasible strategy to develop multifunctional micelleplexes with simultaneous drug conjugation and pDNA condensation, dually responsive drug/gene release and synergistic antitumor efficacy, holding great promise for combinational therapies.
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